A. Field of the Invention
This invention relates to 5,8-dihydro-5-oxopyrido[2,3-d]pyrimidine-6-carboxylic acids useful as antibacterial agents, and to intermediates and processes for their preparation.
B. Description of the Prior Art
The Sterling Drug Inc. Lesher U.S. Pat. No. 3,320,257, issued May 16, 1967, discloses, inter alia, 2-R.sub.2 -4-R.sub.4 -5,8-dihyro-5-oxo-6-Z-8-R-pyrido[2,3-d]pyrimidines where R.sub.2 and R.sub.4 are each hydrogen, lower-alkyl, lower-alkoxy, lower-alkylamino, lower-alkylmercapto, phenylmethyl, phenyloxy, phenylamino or phenylmercapto, Z is carboxy or lower-carbalkoxy, and R is lower-alkyl. The compounds are shown to have antibacterial activity.
The Dainippon Pharmaceutical Co., Ltd. British patent specification No. 1,129,358, published Oct. 2, 1968, discloses as antibacterial agents the 5,8-dihydro-5-oxopyrido[2,3-d]pyrimidine derivatives having the formula 10/10
Wherein R.sub.1 stands for hydrogen or a lower alkyl radical, R.sub.2 stands for hydrogen, a lower alkyl radical, a hydroxy group, a halogen atom, a lower alkoxy radical, an amino group or a lower alkylthio radical, R.sub.3 stands for hydrogen, a lower alkyl radical, a hydroxy group, a lower alkoxy radical, a lower alkylthio group or a radical of formula ##STR1## (in which R' stands for hydrogen, an alkyl radical, a cycloalkyl radical, an amino group, a hydroxyalkyl radical or an alkyl-substituted aminoalkyl radical, R" stands for hydrogen or an alkyl radical or R' and R", together with the nitrogen atom to which they are bonded, form a heterocyclic ring), and R.sub.4 stands for hydrogen or an alkyl radical."
The R. Bellon Lab. German patent application No. DT 2,338,325, published Feb. 7, 1974, is abstracted as follows in the DERWENT "Central Patents Index Alerting Bulletin," Week V7, page B-7, Feb. 7, 1974:
"8-Alkyl-5-oxo-5,8-dihydro-pyrido derivs of (2,3-d) pyrimidine 6-carboxylic acids - antibacterials. PA1 Cpds (I): ##SPC1## PA1 (where R is H, 1-5C alkoxy, 1-5C alkylthio or opt. substd. phenyl or NR.sub.1 R.sub.2 ; R.sub.1 and R.sub.2 are 1-5C alkyl or a heterocyclic 5- or 6-membered ring opt. substd and opt. contg a further hetero-atom) are prepd by reacting 2-R-5-carbalkoxy-5-halo-pyrimidine with R.sub.1 NHCH.sub.2 CH.sub.2 COOEt, cyclising the product to give a 5-oxo-6-carbalkoxy-5,6,7,8-tetrahydro pyrido (2,3-d) pyrimidine, treating this with a halogenating agent, dehalogenating the halogenated product and hydrolysing the ester; when R is NR.sub.1 R.sub.2 this gp. may be introduced before or after the halogenation stage. 1.8.73 as 338325 (clg. 2.8.72 - FR-027876) CO7d 57/20 (7.2.74) BELLON LAB, R."